NIH CRM is a Common Fund-supported initiative that was established in 2010. The efforts of Mahendra Rao, the NIH CRM Director appointed in August 2011, are split between the Center and his intramural laboratory. Since his appointment, Dr. Rao has completed recruitment of the key positions in the laboratory. This comprises two Staff Scientists, Nasir Malik and Jizhong Zou. They have in turn have assisted Dr. Rao in hiring two biologists, Xiantao Wang and Yongquan Luo. The laboratory group has also included quite a few non-permanent staff in the past year, including postdocs and postbacs. Dr. Rao and his laboratory group have generated quite a few scientific publications to date, as outlined below. Due to the extended production process, several of the publications in press since Dr. Rao returned to NIH involved work completed just prior to his appointment. One such publication focused on transgene silencing in engineered human embryonic stem cell lines (MacArthur et al, 2012). These findings demonstrated effective transgene expression when using a combination of insulator sequences and integration at chromosome 13 locus, which would be applicable for lineage development studies. Another study on human embryonic stem cell lines (Schwartz et al, 2012) sought to define factors produced by stromal cells resulting in SDIA during generation of dopaminergic neurons from hESCs. The identification of SDF1a, sFRP1 and VEGFD components in SDIA suggested their potential use in therapeutic intervention for Parkinsons. A collaboration with JHU (Lehmann et al 2012) yielded promising results for drug screening and studies focused on disease mechanisms involving Schwann cells, which are valuable for models but typically underused due to the significant labor involved. In this study, immortalized cell lines derived from primary human SCs retain characteristics of the primary cells, as evaluated by microarray and quantitative reverse transcription PCR assays among others. Results from an astrocyte replacement study (Lepore et al, 2011) built on previous findings showing feasibility of astrocyte transplantation therapy for ALS. This followup study focused on survival, safety and efficacy of hGRPs in the SOD1G93A mouse, and showed robust survival and lack of toxicity but no protective or therapeutic benefit. One of several publications related to iPSC (Ruff et al, 2012) reported findings from a study in which TaqMan PCR technology was used to characterize transcription factors during the reprogramming process. The technology was found to be successful not only for dissecting this process but also for characterizing established iPSC lines. A review of various strategies for generating iPSCs (Parameswaran et al, 2011) focused instead on a recent non-cell autonomous approach to reprogramming corneal progenitors via endogenous transcription factors. A chapter co-written with Ying Liu (Liu et al, 2011) introduced a protocol for gene targeting in human pluripotent stem cells with broad applicability for reporter lines and genetic repair in gene models. Publications resulting from work undertaken following Dr. Raos intramural appointment at NIH include two assessments of iPSC technologies. One editorial (Pal et al, 2012) provided an overview of challenges and advances in iPSC technologies to accompany the articles that they had compiled for that volume, and noted the increasing rapidity of the field and its growing international aspects that will help make translation possible. Issues included achieving zero footprint programming and resolving tumorgenicity. Selected advances addressed by articles included nonintegrating sendai virus-based generation and reprogramming and genetic-based repair and profiling. A review article from Dr. Raos laboratory (Rao et al, 2012) assessed reprogramming methods specifically for their suitability for translational medicine. A single method-based study (Singh et al, 2012) investigated a novel fluorogenic live cell permeant substrate for AP (Live AP Stain) for evaluating the success of reprogrammed cells, to supplement traditional AP staining that prevents further culturing. The stain was found to be an ideal tool, as it did not alter the integrity or characteristics of the cells. And finally, a report on a 2011 NIH summit on cellular therapy for melanoma and other cancers (Stroncek et al, 2012) outlined advances in the field. More traditional therapy such as TIL continues to improve and become more available, while other new gene therapies such as engineered lymphocytes are emerging. These various results are all part of NIH CRMs overarching goal of translating cell-based therapy to the clinic. The laboratory is focused on neural derivatives, and these initial reports showcase processes for efficient manufacture of iPSC and engineering of pluripotent cells.